Phagocytic cells play a vital role in normal host defense against bacterial, fungal, and parasitic infections. The major effector cells involved in destruction of these organisms are polymorphonuclear neutrophils, monocyte-macrophages, and eosinophils. The principal investigator plans to continue studies of the mechanisms whereby these cells encounter, engulf, and destroy potential pathogens. The initial contact of pathogen and phagocytes is made at the surface membrane of the phagocyte. These membranes have been shown to have receptor activity. We will study the topography of receptor activity on the surface of the phagocytic cells and will carefully examine the effect of various factors on receptor topography. The role of motility, chemotactic orientation, and phagocytosis on receptor location will be examined. The influence of receptor location on the ability of phagocytes to encounter, contact, and ingest pathogens will be studied. We will carefully examine mechanisms whereby virulent pathogens avoid destruction by phagocytic cells. In some instances these virulent pathogens have the ability to destroy the phagocytic cells (for example, Streptococcus pyogenes and Entamoeba histolytica). Certain pathogens alter phagocyte metabolism (virulent strains of S. typi) and others destroy potentially toxic products of the phagocyte (S. aureus). Examination of these interactions will aid us in better understanding the dynamic interactions of phagocytic cells and microbial pathogens. Mononuclear cells are an important component of the phagocytic defense against infection. The mechanisms whereby these cell kill are unclear. We have observed that monocytes from patients with chronic granulomatous disease that are ineffective killers of microbes will become effective killers when cultured in vitro. This implies a major change in mechanisms of bactericidal activity. These observations will be pursued and should enable us to better understand normal and abnormal monocyte and macrophage microbicidal activity.